Antisocial Behavior (ASB) and substance use disorders (SUD) develop over time. To be fully understood longitudinal assessment is imperative, particularly for adolescents who have not passed through the age of greatest risk. Component II proposes a 5-year follow-up (Wave-2 assessment) of 285 families of subjects formerly in treatment for substance use disorder (SUD) and conduct disorder (CD) as adolescents and 200 unselected control families, all previously assessed under the current Center (DA-11015). A 10-year follow-up of 400 subjects and their families (200 treatment families and 200 control families) previously assessed under DA-05131 will also be conducted. SUD and comorbid psychopathology will be assessed using the Center's core protocol. An important strength of our study design, which treats the family as the unit of analysis, will enable us to assess the influence of parents on their children (vertical transmission), as well as the influence of siblings on one another (horizontal resemblance) and marital assortment in the development of SUD and ASB. In addition, the oversampling of families selected for extreme phenotypes, in joint analysis with matched control families, provides a powerful analytical design for understanding the familial aggregation and transmission of SUD and ASB in the population. The family study Component will provide important information regarding: 1) family influences underlying vulnerability to SUD and CD; 2) the generality versus specificity of important familial influences on these behaviors; 3) whether influences on the expression of familial liability may be gender-specific; and 4) the identification of family factors that differentiate persistent versus adolescent-limited problem behavior. Such information will be vital to improving phenotype definition, a critical link between the analyses proposed under Component II and our ongoing genetic analyses.